In a study of 170 breast cancer patients we detected significant increases in red blood cell cold agglutinin activities in Stage III, and the histological varieties of apocrine and mucinous carcinoma. Increased lymphocytotoxic activities were also found in breast cancer sera and this activity correlated significantly with red blood cell cold agglutinin levels. This suggests a possible role of these cold reactive antibodies in host defenses in cancer patients. Increased serum I antigen activities were found in Stage IV patients. A RIA method is being developed for precise quantitation of anti-I and I antigen in cancer sera. Under investigation are derivatization of the carbohydrate I antigen by tyramine for the purpose of labeling with 125I and the usefulness of a double antibody method. In the RIA we are planning to characterize immunochemically anti-Ii in cancer sera by oligosaccharide inhibition assays. The results may elucidate the biological role of cancer related anti-Ii and Ii.